Children with cancer experience recurring hospitalizations and isolation during treatment, which affect their school attendance. This study explores experiences of children with cancer, their classmates, and teachers with using the telepresence robot as a learning mediator in the hybrid classroom during treatment periods. 31 children with cancer (aged 7–17 years), 30 teachers, and 118 classmates participated in interviews and 19 h of participant observations were undertaken in nine classrooms. The Agential Realism Theory and Situational Analysis framed the data analysis. There was a single overarching theme, “Telepresence robot didactic,“ and five sub-themes (Telepresence mediated learning, school-home collaboration, hybrid robot teaching, intra-actions in class, and inclusive spatiality). This study advocates the complexity of telepresence robot didactics, emphasizing that numerous human and other factors must intra-act and work simultaneously to achieve optimal learning conditions for children during cancer treatment. This includes considerations such as modality availability for the remote child; the teacher’s understanding of telepresence robot didactic and hybrid learning; the classmate’s ability to involve the remote child in groupwork; the child’s own treatment protocol, the robot’s functionalities, and spatiality in the class. Strategies for use and the systematic surveillance of telepresence robots are needed to ensure that children during cancer treatment do not lag in academic achievement. This study proposes that children with cancer can continue participating in class while hospitalized or isolated and consequently reduce social and academic setbacks.